Implantable medical devices may be used for treatment, curing or remedy of many diseases and conditions in a patient's body. Implantable medical devices may be used for replacing a part of the body (e.g. dental and orthopaedic implants, intraocular lenses), or may be used to correct or restore the structure of an internal tissue or organ (e.g. vascular stents). Implantable medical devices may also be used as drug delivery vehicles.
For example, dental implant systems are widely used for replacing damaged or lost natural teeth. In such systems, a dental fixture is placed in the upper or lower jawbone of a patient in order to replace the natural tooth root. An abutment structure comprising one or several parts is then attached to the fixture in order to build up a core for the part of the prosthetic tooth protruding from the bone tissue, through the soft gingival tissue and into the mouth of the patient. On said abutment, the prosthesis or crown may finally be seated.
For any type of medical implant, biocompatibility is a crucial issue. The risk for foreign body reaction, clot formation and infection, among many other things, must be addressed and minimized in order to avoid adverse effects, local as well as systemic, which may otherwise compromise the health of the patient and/or lead to failure of the implant.
Healing or regeneration of tissue around an implant is vital in order to secure the implant and its long-term functionality. This is particularly the case for load-bearing implants such as dental or orthopaedic implants. For dental fixtures, a strong attachment between the bone and the implant is necessary.
Formation of bone at an implant surface requires the differentiation of precursor cells into secretory osteoblasts to produce unmineralised extracellular matrix (ECM), and the subsequent calcification of this matrix, as described in for instance Anselme K, Osteoblast adhesion on biomaterials, Biomaterials 21, 667-681 (2000). The mechanisms of osseointegration of bone implants have been increasingly elucidated during the last 30 years and today bone implants are particularly designed with respect to material composition, shape and surface properties in order to promote osseointegration. For example, the surface of bone implants is typically provided with a microroughness, which has been demonstrated to affect cell proliferation and differentiation of osteoblast cells, and the local production of growth factors by the cells around a bone implant (Martin J Y et al, Clin Oral Implants Res, March 7(1), 27-37, 1996; Kieswetter K, et al., J Biomed Mater Res, September, 32(1), 55-63, 1996). Further, the surface of a bone implant and may be chemically modified e.g. by coating with bone-like substances such as hydroxyapatite or by application of other bioactive substances that enhance bone formation. It is known that osteoblasts, i.e., bone-forming cells, sense and react to multiple chemical and physical features of the underlying surface. For example, it has been found that a cross-liked collagen layer on a metallic biomaterial improved the cellular response of human osteoblast-like (MG-63) cells (Müller R, Abke J, Schnell E, Scharnweber D, Kujat R, Englert C, Taheri D, Nerlich M, Angele P, Biomaterials 27(22) 059-68 (2006)).
However, a problem with known coatings of e.g. hydroxyapatite or collagen is that the coating may adhere poorly to the implant surface, and may loosen from the implant after implantation, thus compromising its function of enhancing the formation of a strong implant-tissue bond.
For implants intended for contact with soft tissue, such as for example dental implants systems which are to be partially located in the soft gingival tissue, also the compatibility with soft tissue is vital for implant functionality. Typically, after implantation of a dental implant system, an abutment is partially or completely surrounded by gingival tissue. It is desirable that the gingival tissue should heal quickly and firmly around the implant, both for medical and esthetic reasons. A tight sealing between the oral mucosa and the dental implant serves as a soft tissue barrier against the oral microbial environment and is crucial for implant success. This is especially important for patients with poor oral hygiene and/or inadequate bone and mucosal quality. Poor healing or poor attachment between the regenerated tissue and the implant increases the risk for infection and periimplantitis, which may ultimately lead to bone resorption and failure of the implant. Moreover, as the bone is resorbed, the gingiva which is connected to the bone is resorbed as well, resulting in so called “black triangles”, i.e. the absence of gingival tissue between two teeth or implants, which is unaesthetic and may give rise to discomfort for the patient. Worse, extensive gingival resorption can expose the outermost part of the implant.
Many strategies have been proposed to promote tissue healing and integration of soft tissue implants. As an example, WO2009/036117 addresses the problem of poor biological and physiological tolerance of medical devices following implantation, and proposes a biological construct for tissue remodeling which mimics the topographical and physiological environment of a natural healing process. The construct comprises a nano-textured, cyto-compatible, layered, bio-compatible polymeric biomatrix comprising a polymeric bioscaffold seeded with various therapeutic agents. The bioscaffold may comprise pharmaceutical substances and/or other biologically active agents or cells and is designed to release the therapeutic agents in a temporal order that mimics the order of physiological processes that take place during natural organogenesis and tissue regeneration. The polymeric biomatrix can be affixed e.g. by dipping or ultrasonic spray coating, to a delivery vehicle such as a medical device including a stent, vascular graft, shunt, screw, laminar sheet or mesh. However, the complex structure of the construct of WO 2009/036117 would require a relatively complex, multi-step manufacturing process.
Thus, in spite of the advances made in this field in recent years, there is still a need for improved implantable devices which provide improved short-term tissue response and/or improved long-term tissue integration.